A Retrovirus Expressing v-abl and c-myc Induces Plasmacytomas in 100% of Adult Pristane-Primed BALB/c Mice

Abstract

Intraperitoneal mineral oils such as pristane induce plasmacytomas in up to 60% of inbred BALB/c mice over the course of the period of two years ( Potter et al. 1984). The appearance of the tumors can be speeded up dramatically by intraperitoneal injection of Abelson murine leukemia virus (A-MuLV) (Potter et al. 1973). However, the incidence of plasmacytomas does not increase, in part because other tumors, pre-B cell lymphomas and myeloid tumors also arise in this setting. Molecular genetic studies of plasmacytomas have revealed that 100% of these tumors show deregulated expression of the c-myc proto-oncogene (Mushinski 1988). The universal deregulation of c-myc may be necessary, but it appears to be only one step in a multistep scenario leading to plasmacytomagenesis. Recombinant retroviral vectors offer the possibility of studying the cooperation of myc with other oncogenes. So far two oncogenes, in combination with myc, have accelerated plasmacytoma induction as compared to pristane alone. These oncogene combinations, myc+raf (Troppmair et al. 1989, Kurie et al. 1990) or myc+ras (Clynes et al. 1988), in form of retroviruses, accelerated plasmacytoma onset, but did not increase the tumor incidence. Since v-abl apparently cooperated well with deregulated c-myc in A-MuLV-induced tumors in pristane-primed mice, we predicted that a retrovirus which coexpressed v-abl and c-myc would also induce plasmacytomas expeditiously. Thus the protein-encoding portion of c-myc cDNA, under the control of the widely active thymidine kinase promotor, was inserted in the genome of A-MuLV (Largaespada et al. 1990) and injected intraperitonially, either helper-free or with Moloney Murine Leukemia Virus (MoMuLV) helper virus, into immunocompetent inbred BALB/c-AnPt mice which had previously recieved a single injection of 0.5 ml pristane. When ascites accumulated and contained tumor-like cells, the mice were sacrificed and their tumors excised for transplantation, histopathological studies and for DNA and RNA extraction.KeywordsBone Marrow CellHelper VirusKappa Light ChainViral Integration SiteImmunoglobulin Heavy Chain RearrangementThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.